Aberrant Cell Proliferation by Enhanced Mitochondrial Biogenesis via mtTFA in Arsenical Skin Cancers

Lee, Chih Hung; Wu, Shengjun; Hong, Chien Hui; Liao, Wei‐Ting; Wu, Chieh‐Shan; Chen, Gwo Shing; Wei, Yau Huei; Yu, Hsin Su

doi:10.1016/j.ajpath.2011.01.056

Cited by 87 publications

(78 citation statements)

References 41 publications

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“…Beside ovarian cancer, TFAM upregulation is also observed in breast, colorectal, bladder, endometrial and arsenic induced skin cancer with subsequent increase in MtBIO and cellular proliferation. Many study show similar results both in experimental and clinical settings [71][72][73][74][75][76][77]. Such findings suggest TFAM as one of the most important therapeutic targets in chemoresistant ovarian cancer.…”

Section: Mitochondrial Transcription Factor a (Tfam)supporting

confidence: 68%

“…Upon import to mitochondria it performs multiple regulatory functions including mtDNA transcription, maintenance of mtDNA looping, coating and packaging (mitochondrial nucleoids) [59,69,70]. It contains facets for binding nuclear respiratory factor (NRF) 1 and NRF2 which act on the promoter of D-loop region leading to increased mtDNA copy number [71]. Significant overexpression of TFAM was observed in human serous ovarian cancer in association with poor 5-years survival.…”

Section: Mitochondrial Transcription Factor a (Tfam)mentioning

confidence: 99%

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Anticancer Strategy Targeting Mitochondrial Biogenesis in Ovarian Cancer

Uddin¹,

Kim²,

Suh³

et al. 2014

J Cancer Sci Ther

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IntroductionOvarian cancer is the most lethal gynecologic malignancy worldwide typically in the post-menopausal women and 5 th leading cause of death in the United States [1][2][3]. About 80% of women are diagnosed at the advanced-stage of disease and have poor prognosis. The 5-year overall survival rate is 45% or below [4][5][6]. Despite the first complete response after the front-line platinum-based chemotherapeutic drugs [7,8], approximately 25% patients suffer from relapse within 6 months who are thought, by definition, to have a chemoresistance [9][10][11][12]. Combination of platinum and other drugs might improve the survival rate [13], but is not out of the danger of additive toxicity [14].Several genetic alterations have been observed in ovarian cancer, involving deactivation mutations in tumor suppressor genes, such as p53, BRCA1 and BRCA2, and activation mutation and/or amplification of proto-oncogenes, like c-MYC, KRAS and AKT [15]. Recent genomic analysis of The Cancer Genome Atlas reported mutations in p53 gene in 96% of 316 cases of high-grade ovarian serous carcinoma (HGOSC) [16]. Other important genetic changes affect phosphatidyinositol-3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) cascade. The mTOR plays a central role in energy metabolism, cell growth/division through macromolecular synthesis and is found to be activated in ovarian cancer [6], which indicates a close relationship between genetic alteration and energy metabolism. It was observed that hexokinase (HK) II, the rate limiting initial enzyme in glycolysis, is overexpressed in ovarian cancer [12]. The genetic alterations and subsequent metabolic remodeling have been found to be associated with the chemoresistance [17], such as association of rictor (mTORC2 component) with resistance to cisplatin [2]. Cisplatin-induced caspase activation causing PTEN cleavage has also been reported as a potential mechanism of chemoresistance in ovarian cancer [18].Mitochondria is a well-adapted endosymbiotic intracellular organelles, became efficient for energy production through-out the course of evolution [19]. They are critical for survival and proliferation of living organisms under aerobic conditions and produce ATP through oxidative phosphorylation (OXPHOS) [20]. Beyond the conventional function they have crucial role in certain neurodegenerative diseases and cancer [21][22][23]. Cellular proliferation largely depends on mitochondrial amount, governed by the process of MtBIO [20]. MtBIO is the production of daughter mitochondria usually from previously existed one through a division process of called fission, subsequent growth, and maintenance by fusion and autophagy of mitochondria (mitophagy) [24]. Currently it has been observed that MtBIO is associated with cancer chemoresistance [25,26] through the modulation of associated proteins such as methylation-controlled J-protein (MCJ, also known as DNAJC15) [25,27], prohibitin 1 (PHB-1) [28][29][30], myeloid cell leukemia sequence 1 (MCL-1) [31,32] etc. in ovarian cancer. Thus it can be s...

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Section: Mitochondrial Transcription Factor a (Tfam)supporting

confidence: 68%

Section: Mitochondrial Transcription Factor a (Tfam)mentioning

confidence: 99%

Anticancer Strategy Targeting Mitochondrial Biogenesis in Ovarian Cancer

Uddin¹,

Kim²,

Suh³

et al. 2014

J Cancer Sci Ther

View full text Add to dashboard Cite

show abstract

“…To confirm the results for mitochondrial DNA content, we studied the expression of COX6c. This protein is localized on the mitochondrial inner membrane and is considered to be a reliable marker of mitochondrial content (36,37). The COX6c protein is expressed in trophoblastic and mesenchymal cells, with a stronger expression in trophoblastic cells.…”

Section: Mitochondrial Contentmentioning

confidence: 99%

Involvement of estrogen-related receptor-γ and mitochondrial content in intrauterine growth restriction and preeclampsia

Poidatz

Santos

Duval

et al. 2015

Fertility and Sterility

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“…In particular, it has been demonstrated that PGC1a may function as a co-activator of androgen receptor thus favoring the proliferation of prostate cancer [13]. In cutaneous carcinoma an increased expression of PGC1a, NRF-1 and TFAM was found pointing to an implication of mitochondrial biogenesis as crucial event in tumor cell growth [15]. In line with its pro-tumour activity, PGC1a loss protects mice from colon and liver carcinogenesis induced by azoxymethane and diethylnitrosamine respectively, by a mechanism involving the inhibition of lipogenesis-stimulated tumor The peroxisome proliferator activated receptor gamma co-activator 1 alpha (PGC1a) is an inducible transcriptional co-activator with direct function in the induction of mitochondrial biogenesis.…”

Section: Introductionmentioning

confidence: 97%